Flexible circuit electrode array for improved layer adhesion

ABSTRACT

Present invention is a method of improving circadian rhythms in blind people by stimulation the visual neural system. Ideally a retinal prosthesis of the type used to restore vision can be used to restore normal circadian rhythms. Additionally, brightness on the prosthesis can be increased in the morning and decreased in the evening to stimulate normal Circadian rhythms. Alternatively, if a retinal prosthesis is not preferable, the retina can be stimulated externally, during the day and not at night. While such eternal stimulation can not produced artificial vision, it can stimulate normal circadian rhythms.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.11/293,400, “Visual Prosthesis for Improved Circadian Rhythms and Methodof Improving the Circadian Rhythms”, filed Dec. 1, 2005 now U.S. Pat.No. 8,068,913 issued Nov. 29, 2011, the disclosure of which isincorporated herein by reference, and which claims the benefit of U.S.Provisional Application No. 60/633,190 “Visual Prosthesis for ImprovedCircadian Rhythms”, filed Dec. 3, 2004, the disclosure of which isincorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was made with government support under grant No.R24EY12893-01, which has been awarded by the National Institutes ofHealth. The government has certain rights in the invention.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention is generally directed to neural stimulation andmore specifically to neural stimulation of the visual system forimproved circadian rhythms and a method of improving the circadianrhythms.

2. Background of the Invention

In 1755 LeRoy passed the discharge of a Leyden jar through the orbit ofa man who was blind from cataract and the patient saw “flames passingrapidly downwards.” Ever since, there has been a fascination withelectrically elicited visual perception. The general concept ofelectrical stimulation of retinal cells to produce these flashes oflight or phosphenes has been known for quite some time. Based on thesegeneral principles, some early attempts at devising prosthesis foraiding the visually impaired have included attaching electrodes to thehead or eyelids of patients. While some of these early attempts met withsome limited success, these early prosthetic devices were large, bulkyand could not produce adequate simulated vision to truly aid thevisually impaired.

In the early 1930's, Foerster investigated the effect of electricallystimulating the exposed occipital pole of one cerebral hemisphere. Hefound that, when a point at the extreme occipital pole was stimulated,the patient perceived a small spot of light directly in front andmotionless (a phosphene). Subsequently, Brindley and Lewin (1968)thoroughly studied electrical stimulation of the human occipital(visual) cortex. By varying the stimulation parameters, theseinvestigators described in detail the location of the phosphenesproduced relative to the specific region of the occipital cortexstimulated. These experiments demonstrated: (1) the consistent shape andposition of phosphenes; (2) that increased stimulation pulse durationmade phosphenes brighter; and (3) that there was no detectableinteraction between neighboring electrodes which were as close as 2.4 mmapart.

As intraocular surgical techniques have advanced, it has become possibleto apply stimulation on small groups and even on individual retinalcells to generate focused phosphenes through devices implanted withinthe eye itself. This has sparked renewed interest in developing methodsand apparati to aid the visually impaired. Specifically, great efforthas been expended in the area of intraocular retinal prosthesis devicesin an effort to restore vision in cases where blindness is caused byphotoreceptor degenerative retinal diseases such as retinitis pigmentosaand age related macular degeneration which affect millions of peopleworldwide.

Neural tissue can be artificially stimulated and activated by prostheticdevices that pass pulses of electrical current through electrodes onsuch a device. The passage of current causes changes in electricalpotentials across visual neuronal membranes, which can initiate visualneuron action potentials, which are the means of information transfer inthe nervous system.

Based on this mechanism, it is possible to input information into thenervous system by coding the information as a sequence of electricalpulses which are relayed to the nervous system via the prostheticdevice. In this way, it is possible to provide artificial sensationsincluding vision.

One typical application of neural tissue stimulation is in therehabilitation of the blind. Some forms of blindness involve selectiveloss of the light sensitive transducers of the retina. Other retinalneurons remain viable, however, and may be activated in the mannerdescribed above by placement of a prosthetic electrode device on theinner (toward the vitreous) retinal surface (epiretial). This placementmust be mechanically stable, minimize the distance between the deviceelectrodes and the visual neurons, and avoid undue compression of thevisual neurons.

Dawson and Radtke stimulated cat's retina by direct electricalstimulation of the retinal ganglion cell layer. These experimentersplaced nine and then fourteen electrodes upon the inner retinal layer(i.e., primarily the ganglion cell layer) of two cats. Their experimentssuggested that electrical stimulation of the retina with 30 to 100 μAcurrent resulted in visual cortical responses. These experiments werecarried out with needle-shaped electrodes that penetrated the surface ofthe retina (see also U.S. Pat. No. 4,628,933 to Michelson).

In U.S. Pat. No. 3,699,970 “Striate Cortex Stimulator” to Giles SkeyBrindley et al. an implantable device is disclosed comprising aplurality of electrodes for stimulating the striate cortex.

In U.S. Pat. No. 4,487,652 “Slope. Etch of Polyimide” to Carl W. Amgrena semiconductor having an insulating layer overlying a metal layer isdisclosed, wherein the insulator comprises an upper oxide layer, anintermediate polyimide layer, and a lower oxide layer in contact withthe metal layer, a method for etching a via from an upper surface of thepolyimide layer to the metal layer comprising the steps of applyingphotoresist; etching an opening from an upper surface of the photoresistlayer to the upper oxide layer at a location for forming the via so thatan upper surface of the upper oxide layer is exposed at the vialocation; heating the photoresist to cause a more gradual slope of thephotoresist layer from the upper surface of the upper oxide layer at thevia location to the upper surface of the photoresist layer; applyingreactive ion etchant with a predetermined selectivity betweenphotoresist and oxide to transfer the slope of the photoresist layer tothe upper oxide layer at a predetermined ratio; and applying a reactiveion etchant with a predetermined selectivity between oxide and polyimideto transfer the slope of the upper oxide layer to the polyimide layer ata predetermined ratio, whereby the lower oxide layer is simultaneouslyetched to expose the metal layer at the via location.

In U.S. Pat. No. 4,573,481 “Implantable Electrode Array” to Leo A.Bullara an electrode assembly for surgical implantation on a nerve ofthe peripheral nerve system is disclosed.

In U.S. Pat. No. 4,628,933 “Method and Apparatus for Visual Prosthesis”to Robin P. Michelson a visual prosthesis for implantation in the eye inthe optical pathway thereof is disclosed.

In U.S. Pat. No. 4,837,049 “Method of Making an Electrode Array” toCharles L. Byers et al. a very small electrode array which penetratesnerves for sensing electrical activity therein or to provide electricalstimulation is disclosed.

In U.S. Pat. No. 4,996,629 “Circuit Board with Self-SupportingConnection Between Sides” to Robert A. Christiansen et al. a coppersupporting sheet is disclosed having vias for connecting semiconductorchips to surface mount components. A laminate of polyimide has viascorresponding to the supporting layer vias with copper covering thosevias.

In U.S. Pat. No. 5,108,819 “Thin Film Electrical Component” to James W.Heller a thin film electrical component is disclosed comprising a rigidglass carrier plate, a substrate bonded to the rigid glass carrierplate, the substrate comprising a polyimide establishing a bond with therigid glass carrier plate that is broken upon immersion of the substrateand the rigid glass carrier plate in one of a hot water bath and a warmtemperature physiologic saline bath to release the polymer fromattachment to the rigid glass carrier plate, and means for providing anelectrical circuit, the providing means being bonded to the substrateand undisrupted during release of the substrate from attachment to therigid glass carrier plate.

In U.S. Pat. No. 5,109,844 “Retinal Microstimulation” to Eugene. de JuanJr. et al. a method for stimulating a retinal ganglion cell in a retinawithout penetrating the retinal basement membrane at the surface of theretina is disclosed.

In U.S. Pat. No. 5,178,957 “Noble Metal-Polymer Composites and FlexibleThin-Film Conductors Prepared Therefrom” to Vasant V. Kolpe a compositearticle is disclosed comprising a polymeric support selected from thegroup consisting of a polyimide, polyethylene terephthalate, andpolyester-ether block copolymer having a noble metal deposited directlyonto at least one surface, wherein said deposited metal exhibits a peelforce of at least about 0.05 kg per millimeter width after 24 hourboiling saline treatment.

In U.S. Pat. No. 5,215,088 “Three-Dimensional Electrode Device” toRichard A. Norman et al. a three-dimensional electrode device forplacing electrodes in close proximity to cell lying at least about 1000microns below a tissue surface is disclosed.

In U.S. Pat. No. 5,935,155 “Visual Prosthesis and Method of Using Same”to Mark S. Humayun et al. a visual prosthesis is disclosed comprising acamera for receiving a visual image and generating a visual signaloutput, retinal tissue stimulation circuitry adapted to be operativelyattached to the user's retina, and wireless communication circuitry fortransmitting the visual signal output to the retinal tissue stimulationcircuitry within the eye.

In U.S. Pat. No. 6,071,819 “Flexible Skin Incorporating MEMS Technology”to Yu-Chong Tai a method of manufacturing a flexible microelectronicdevice is disclosed comprising first etching a lower side of a waferusing a first caustic agent; depositing a first layer of aluminum on anupper side of the wafer; patterning the first layer of aluminum;depositing a first layer of polyimide on the upper side of the wafer,covering the first layer of aluminum; depositing a second layer ofaluminum on the upper side of the wafer, covering the first layer ofpolyimide; depositing a second layer of polyimide on the upper side ofthe wafer, covering the second layer of aluminum; depositing a thirdlayer of aluminum on the lower side of the wafer; patterning the thirdlayer of aluminum; second etching the lower side of the wafer using thethird layer of aluminum as a mask and the first layer of aluminum as anetch stop and using a less caustic agent than said first caustic agent,such that the wafer is divided into islands with gaps surrounding eachisland; and depositing a third layer of polyimide on the lower side ofthe wafer, such that the gaps are at least partially filled.

In U.S. Pat. No. 6,324,429 “Chronically Implantable Retinal Prosthesis”to Doug Shire et al. an apparatus is disclosed which is in contact withthe inner surface of the retina and electrically stimulates at least aportion of the surface of the retina.

In U.S. Pat. No. 6,374,143 “Modiolar Hugging Electrode Array” to PeterG. Berrang et al. a cochlear electrode array for stimulating auditoryprocesses is disclosed.

In U.S. Pat. No. 6,847,847 “Retina Implant Assembly and Methods forManufacturing the Same” to Wilfried Nisch et al. a retina implant isdisclosed comprising a chip in subretinal contact with the retina and areceiver coil for inductively coupling there into electromagneticenergy.

In U.S. patent application Ser. No. 20010037061 A1, “Microcontactstructure for neuroprostheses for implantation on nerve tissue andmethod therefore” to Rolf Eckmiller et al. a four layer microcontactstructure is disclosed in which the active connection between themicrocontact structure and the nerve tissue is brought about byelectrical stimulation. The layer adjacent to the nerve tissue to bestimulated is composed of the polymer polyimide and contains penetratingelectrodes made of platinum which forms the adjoining layer. Therefollows a further layer of the polyimide and a layer of the polymerpolyurethane. Polyurethane has the property of thermal expansionrelative to polyimide.

In U.S. patent application Ser. No. 2003/0158588 A1 “Minimal InvasiveRetinal Prosthesis” to John F. Rizzo et al. a retinal prosthesis isdisclosed comprising an RF coil attached to the outside of and movingwith an eye to receive power from an external power source; electroniccircuitry attached to and moving with the eye and electrically connectedto the RF coil; a light sensitive array electrically connected to theelectronic circuitry and located within the eye for receiving incidentlight and for generating an electrical signal in response to theincident light; and a stimulating array abutting a retina of the eye andelectrically connected to the electronic circuitry to stimulate retinaltissue in response to the electrical signal from the light sensitivearray. A supporting silicone substrate has a polyimide layer spun ontoits surface and cured. The copper or chrome/gold conducting layer isthen added and patterned using wet chemical etching or a photoresistlift-off process. Next, a second polyimide layer is spun on, and theregions where circuit components are to be added are exposed byselective dry etching or laser ablation of the upper polyimide layer inthe desired areas. Finally, the completed components are removed fromtheir supporting substrate.

Eugene de Juan Jr. et al. at Duke University Eye Center inserted retinaltacks into retinas in an effort to reattach retinas that had detachedfrom the underlying choroid, which is the source of blood supply for theouter retina and thus the photoreceptors. See for example E. de JuanJr., et al., “Retinal tacks”, Am J Ophthalmol. 1985 Mar. 15; 99(3):272-4.

Hansjoerg Beutel et al. at the Fraunhofer Institute for BiomedicalEngineering IBMT demonstrated the bonding of a gold ball by force,temperature, and ultrasound onto an aluminum metal layer. See forexample Hansjoerg Beutel, Thomas Stieglitz, Joerg-Uwe Meyer: “VersatileMicroflex-Based Interconnection Technique,” Proc. SPIE Conf. on SmartElectronics and MEMS, San Diego, Calif., March 1998, vol. 3328, pp174-182. A robust bond can be achieved in this way. However,encapsulation proves difficult to effectively implement with thismethod. Gold, while biocompatible, is not completely stable under theconditions present in an implant device since it dissolves byelectromigration when implanted in living tissue and subject to anelectric current. See for example Marcel Pourbaix: “Atlas ofElectrochemical Equilibria in Aqueous Solutions”, National Associationof Corrosion Engineers, Houston, 1974, pp 399-405.

A system for retinal stimulation comprising a polyimide-based electrodesbeing coated with platinum black are described by Andreas Schneider andThomas Stieglitz. See for example Andreas Schneider, Thomas Stieglitz:“Implantable Flexible Electrodes for Functional Electrical Stimulation”,Medical Device Technology, 2004.

It is known that circadian rhythms drive our body's natural cycles ofwake and sleep. The hormone melatonin is produced in increasingquantities in the evening and lesser quantities in the morning. Blindpeople generally do not have normal circadian rhythms and do notproduced extra melatonin in the evening. Hence, the perception of light,at least in part, drives the circadian rhythm and the production ofmelatonin.

SUMMARY OF THE INVENTION

Present invention is a method of improving circadian rhythms in blindpeople by stimulation the visual neural system. Ideally a retinalprosthesis of the type used to restore vision can be used to restorenormal circadian rhythms. Additionally, brightness on the prosthesis canbe increased in the morning and decreased in the evening to stimulatenormal circadian rhythms. Alternatively, if a retinal prosthesis is notpreferable, the retinal can be stimulated externally, during the day andnot at night. While such eternal stimulation can not produced artificialvision, it can stimulate normal circadian rhythms.

One aspect of the present invention is a visual prosthesis forstimulating circadian rhythms comprising at least one electrode suitablefor electrically stimulating visual neurons;

an electrical driver for applying a controlled electrical potential onsaid electrode; and

a timer for controlling activation of said electrical driver.

Another aspect of the present invention is a flexible circuit electrodearray for improving circadian rhythms, comprising

an insulating polymer layer;

at least one trace containing a base conducting layer, an intermediateconducting layer and a top conducting layer, embedded in said insulatingpolymer layer; and

at least one electrode connected to said conducting layer of said tracethrough a via in said insulating polymer layer and said top coat layer.

Another aspect of the intention is a method of using a flexible circuitelectrode array for manufacturing a visual prosthesis for increasing themelatonin levels at night.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a perspective view of the implanted portion of thepreferred retinal prosthesis including a twist in the array to reducethe width of a scleratomy and a sleeve to promote sealing of thescleratomy.

FIG. 2 depicts a perspective view of the implanted portion of theretinal prosthesis showing the fan tail in more detail.

FIGS. 3 a-3 e depicts a perspective view of molds for forming theflexible circuit array in a curve.

FIG. 4 depicts a perspective view of the invention with ribs to helpmaintain curvature and prevent retinal damage.

FIG. 5 depicts a top view of a body comprising a flexible circuitelectrode array, a flexible circuit cable and a bond pad before it isfolded and attached to the implanted portion.

FIG. 6 depicts a top view of a body comprising a flexible circuitelectrode array, a flexible circuit cable and a bond pad after it isfolded.

FIG. 7 depicts a top view of a body comprising a flexible circuitelectrode array, a flexible circuit cable and a bond pad after it isfolded with a protective skirt.

FIG. 8 depicts a cross-sectional view of a flexible circuit array with aprotective skirt bonded to the back side of the flexible circuit array.

FIG. 9 depicts a cross-sectional view of a flexible circuit array with aprotective skirt bonded to the front side of the flexible circuit array.

FIG. 10 depicts a cross-sectional view of a flexible circuit array witha protective skirt bonded to the back side of the flexible circuit arrayand molded around the edges of the flexible circuit array.

FIG. 11 depicts a cross-sectional view of a flexible circuit array witha protective skirt bonded to the back side of the flexible circuit arrayand molded around the edges of the flexible circuit array and flush withthe front side of the array.

FIG. 12 depicts a top view of the flexible circuit electrode array.

FIG. 13 depicts a perspective view of a part of the flexible circuitelectrode array.

FIG. 14 is a graph of experimental data showing patient PB preoperative.

FIG. 15 is a graph of experimental data showing patient PBpostoperative.

FIG. 16 is a graph of experimental data showing patient TB preoperative.

FIG. 17 is a graph of experimental data showing patient TBpostoperative.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 shows a perspective view of the implanted portion of thepreferred retinal prosthesis. A flexible circuit electrode array 10 ismounted by a retinal tack or similar means to the epiretinal surface.The flexible circuit electrode array 10 is electrically coupled by aflexible circuit cable 12, which pierces the sclera and is electricallycoupled to an electronics package 14, external to the sclera.

The electronics package 14 is electrically coupled to a secondaryinductive coil 16. Preferably the secondary inductive coil 16 is madefrom wound wire. Alternatively, the secondary inductive coil 16 may bemade from a flexible circuit polymer sandwich with wire traces depositedbetween layers of flexible circuit polymer. The electronics package 14and secondary inductive coil 16 are held together by a molded body 18.The molded body 18 may also include suture tabs 20. The molded body 18narrows to form a strap 22 which surrounds the sclera and holds themolded body 18, secondary inductive coil 16, and electronics package 14in place. The molded body 18, suture tabs 20 and strap 22 are preferablyan integrated unit made of silicone elastomer. Silicone elastomer can beformed in a pre-curved shape to match the curvature of a typical sclera.However, silicone remains flexible enough to accommodate implantationand to adapt to variations in the curvature of an individual sclera. Thesecondary inductive coil 16 and molded body 18 are preferably ovalshaped. A strap 22 can better support an oval shaped coil 16.

The implanted portion of the retinal prosthesis may include theadditional feature of a gentle twist or fold 48 in the flexible circuitcable 12, where the flexible circuit cable 12 passes through the sclera(scleratomy). The twist 48 may be a simple sharp twist, or fold; or itmay be a longer twist, forming a tube. While the tube is rounder, itreduces the flexibility of the flexible circuit cable 12. A simple foldreduces the width of the flexible circuit cable 12 with only minimalimpact on flexibility.

Further, silicone or other pliable substance may be used to fill thecenter of the tube or fold 48 formed by the twisted flexible circuitcable 12. Further it is advantageous to provide a sleeve or coating 50that promotes healing of the scleratomy. Polymers such as polyimide,which may be used to form the flexible circuit cable 12 and flexiblecircuit electrode array 10, are generally very smooth and do not promotea good bond between the flexible circuit cable 12 and scleral tissue. Asleeve or coating 50 of polyester, collagen, silicone, Gore-Tex® orsimilar material would bond with scleral tissue and promote healing. Inparticular, a porous material will allow scleral tissue to grow into thepores promoting a good bond.

The entire implant is attached to and supported by the sclera. An eyemoves constantly. The eye moves to scan a scene and also has a jittermotion to improve acuity. Even though such motion is useless in theblind, it often continues long after a person has lost their sight. Byplacing the device under the rectus muscles with the electronics package14 in an area of fatty tissue between the rectus muscles, eye motiondoes not cause any flexing which might fatigue, and eventually damage,the device.

Human vision provides a field of view that is wider than it is high.This is partially due to fact that we have two eyes, but even a singleeye provides a field of view that is approximately 90° high and 140° to160° degrees wide. It is therefore, advantageous to provide a flexiblecircuit electrode array 10 that is wider than it is tall. This isequally applicable to a cortical visual array. In which case, the widerdimension is not horizontal on the visual cortex, but corresponds tohorizontal in the visual scene.

FIG. 2 shows a side view of the implanted portion of the retinalprosthesis, in particular, emphasizing the fan tail 24. When implantingthe retinal prosthesis, it is necessary to pass the strap 22 under theeye muscles to surround the sclera. The secondary inductive coil 16 andmolded body 18 must also follow the strap 22 under the lateral rectusmuscle on the side of the sclera. The implanted portion of the retinalprosthesis is very delicate. It is easy to tear the molded body 18 orbreak wires in the secondary inductive coil 16. In order to allow themolded body 18 to slide smoothly under the lateral rectus muscle, themolded body 18 is shaped in the form of a fan tail 24 on the endopposite the electronics package 14.

The flexible circuit electrode array 10 is a made by the followingprocess. First, a layer of polymer is applied to a supporting substrate(not part of the array) such as glass. The polymer layer or films of thepresent invention can be made, for example, any one of the variouspolyfluorocarbons, polyethylene, polypropylene, polyimide, polyamide,silicone or other biologically inert organic polymers. Layers may beapplied by spinning, meniscus coating, casting, sputtering or otherphysical or chemical vapor deposition, or similar process. Subsequently,a metal layer is applied to the polymer. The metal is patterned byphotolithographic process. Preferably, a photoresist is applied andpatterned by photolithography followed by a wet etch of the unprotectedmetal. Alternatively, the metal can be patterned by lift-off technique,laser ablation or direct write techniques.

It is advantageous to make the metal thicker at the electrode and bondpad to improve electrical continuity. This can be accomplished throughany of the above methods or electroplating. Then, the top layer ofpolymer is applied over the metal. Openings in the top layer forelectrical contact to the electronics package 14 and the flexiblecircuit electrode array 10 may be accomplished by laser ablation orreactive ion etching (RIE) or photolithograph and wet etch. Making theelectrode openings in the top layer smaller than the electrodes promotesadhesion by avoiding delaminating around the electrode edges.

The pressure applied against the retina by the flexible circuitelectrode array 10 is critical. Too little pressure causes increasedelectrical resistance between the array and retina. Common flexiblecircuit fabrication techniques such as photolithography generallyrequire that a flexible circuit electrode array 10 be made flat. Sincethe retina is spherical, a flat array will necessarily apply morepressure near its edges, than at its center. With most polymers, it ispossible to curve them when heated in a mold. By applying the rightamount of heat to a completed array, a curve can be induced that matchesthe curve of the retina. To minimize warping, it is often advantageousto repeatedly heat the flexible circuit in multiple molds, each with adecreasing radius. FIG. 3 illustrates a series of molds according to thepreferred embodiment. Since the flexible circuit will maintain aconstant length, the curvature 30 must be slowly increased along thatlength. As the curvature 30 increases in successive molds (FIGS. 3 a-3e) the straight line length between ends 32 and 34, must decrease tokeep the length along the curvature 30 constant, where mold 3Eapproximates the curvature 30 of the retina or other desired neuraltissue. The molds provide a further opening 36 for the flexible circuitcable 12 of the array to exit the mold without excessive curvature.

It should be noted that suitable polymers include thermoplasticmaterials and thermoset materials. While a thermoplastic material willprovide some stretch when heated a thermoset material will not. Thesuccessive molds are, therefore, advantageous only with a thermoplasticmaterial. A thermoset material works as well in a single mold as it willwith successive smaller molds. It should be noted that, particularlywith a thermoset material, excessive curvature 30 in three dimensionswill cause the polymer material to wrinkle at the edges. This can causedamage to both the array and the retina. Hence, the amount of curvature30 is a compromise between the desired curvature, array surface area,and the properties of the material.

Referring to FIG. 4, the edges of the polymer layers are often sharp.There is a risk that the sharp edges of a flexible circuit will cut intodelicate retinal tissue. It is advantageous to add a soft material, suchas silicone, to the edges of a flexible circuit electrode array 10 toround the edges and protect the retina. Silicone around the entire edgemay make the flexible circuit less flexible. It is advantageous toprovide silicone bumpers or ribs to hold the edge of the flexiblecircuit electrode array 10 away from the retinal tissue. Curvature fitsagainst the retina. The leading edge 44 is most likely to cause damageand is therefore fit with molded silicone bumper. Also, edge 46, wherethe array lifts off the retina can cause damage and should be fit with abumper. Any space along the side edges of curvature may cause damage andmay be fit with bumpers as well. It is also possible for the flexiblecircuit cable 12 of the electrode array to contact the retina. It is,therefore, advantageous to add periodic bumpers along the cable 12.

It is also advantageous to create a reverse curve or service loop in theflexible circuit cable 12 of the flexible circuit electrode array 10 togently lift the flexible circuit cable 12 off the retina and curve itaway from the retina, before it pierces the sclera at a scleratomy. Itis not necessary to heat curve the service loop as described above, theflexible circuit electrode array 10 can simply be bent or creased uponimplantation. This service loop reduces the likelihood of any stressexerted extraocularly from being transmitted to the electrode region andretina. It also provides for accommodation of a range of eye sizes.

With existing technology, it is necessary to place the implanted controlelectronics outside of the sclera, while a retinal flexible circuitelectrode array 10 must be inside the sclera in order to contact theretina. The sclera must be cut through at the pars plana, forming ascleratomy, and the flexible circuit passed through the scleratomy. Aflexible circuit is thin but wide. The more electrode wires, the widerthe flexible circuit must be. It is difficult to seal a scleratomy overa flexible circuit wide enough to support enough wires for a highresolution array.

FIG. 5 shows a body 1 containing the flexible circuit electrode array10, the flexible circuit cable 12 and the interconnection pad 52 priorto folding and attaching the array to the electronics package 14. At oneend of the flexible circuit cable 12 is an interconnection pad 52 forconnection to the electronics package 14. At the other end of theflexible circuit cable 12 is the flexible circuit electrode array 10.Further, an attachment point 54 is provided near the flexible circuitelectrode array 10. A retina tack (not shown) is placed through theattachment point 54 to hold the flexible circuit electrode array 10 tothe retina. A stress relief 55 is provided surrounding the attachmentpoint 54. The stress relief 55 may be made of a softer polymer than theflexible circuit, or it may include cutouts or thinning of the polymerto reduce the stress transmitted from the retina tack to the flexiblecircuit electrode array 10. The flexible circuit cable 12 is formed in adog leg pattern so than when it is folded at fold 48 it effectivelyforms a straight flexible circuit cable 12 with a narrower portion atthe fold 48 for passing through the scleratomy.

FIG. 6 shows the flexible circuit electrode array 10 after the flexiblecircuit cable 12 is folded at the fold 48 to form a narrowed section.The flexible circuit cable 12 may include a twist or tube shape as well.With a retinal prosthesis as shown in FIG. 1, the interconnection pad 52for connection to the electronics package 14 and the flexible circuitelectrode array 10 are on opposite side of the flexible circuit. Thisrequires patterning, in some manner, both the base polymer layer and thetop polymer layer. By folding the flexible circuit cable 12 of theflexible circuit electrode array 10, the openings for the bond pad 52and the electrodes are on the top polymer layer and only the top polymerlayer needs to be patterned.

Also, since the narrowed portion of the flexible circuit cable 12pierces the sclera, shoulders formed by opposite ends of the narrowedportion help prevent the flexible circuit cable 12 from moving throughthe sclera. It may be further advantageous to add ribs or bumps ofsilicone or similar material to the shoulders to further prevent theflexible circuit cable 12 from moving through the sclera.

Further it is advantageous to provide a suture tab 56 in the flexiblecircuit body near the electronics package 14 to prevent any movement inthe electronics package 14 from being transmitted to the flexiblecircuit electrode array 10. Alternatively, a segment of the flexiblecircuit cable 12 can be reinforced to permit it to be secured directlywith a suture.

An alternative to the bumpers described in FIG. 4, is a skirt ofsilicone or other pliable material as shown in FIGS. 5 to 7. A skirt 60covers the flexible circuit electrode array 10, and extends beyond itsedges. It is further advantageous to include windows 62 adjacent to theattachment point 54 to spread any stress of attachment over a largerarea of the retina. There are several ways of forming and bonding theskirt 60. The skirt 60 may be directly bonded through surface activationor indirectly bonded using an adhesive as shown in FIG. 7.

Alternatively, a flexible circuit electrode array 10 may be layeredusing different polymers for each layer. Using too soft of a polymer mayallow too much stretch and break the metal traces. Too hard of a polymermay cause damage to delicate neural tissue. Hence a relatively hardpolymer, such a polyimide may be used for the bottom layer and arelatively softer polymer such a silicone may be used for the top layerincluding an integral skirt to protect delicate neural tissue.

The simplest solution is to bond the skirt 60 to the back side away fromthe retina of the flexible circuit electrode array 10 as shown in FIG.8. While this is the simplest mechanical solution, sharp edges of theflexible circuit electrode array 10 may contact the delicate retinatissue. Bonding the skirt to the front side toward the retina of theflexible circuit electrode array 10, as shown in FIG. 9, will protectthe retina from sharp edges of the flexible circuit electrode array 10.However, a window 62 must be cut in the skirt 60 around the electrodes.Further, it is more difficult to reliably bond the skirt 60 to theflexible circuit electrode array 10 with such a small contact area. Thismethod also creates a space between the electrodes and the retina whichwill reduce efficiency and broaden the electrical field distribution ofeach electrode. Broadening the electric field distribution will limitthe possible resolution of the flexible circuit electrode array 10.

FIG. 8 shows another structure where the skirt 60 is bonded to the backside of the flexible circuit electrode array 10, but curves around anysharp edges of the flexible circuit electrode array 10 to protect theretina. This gives a strong bond and protects the flexible circuitelectrode array 10 edges. Because it is bonded to the back side andmolded around the edges, rather than bonded to the front side, of theflexible circuit electrode array 10, the portion extending beyond thefront side of the flexible circuit electrode array 10 can be muchsmaller. This limits any additional spacing between the electrodes andthe retinal tissue.

FIG. 9, shows a flexible circuit electrode array 10 similar to FIG. 10,with the skirt 60, flush with the front side of the flexible circuitelectrode array 10 rather than extending beyond the front side. Whilethis is more difficult to manufacture, it does not lift the electrodesoff the retinal surface as with the array in FIG. 10. It should be notedthat FIGS. 8, 10, and 11 show skirt 60 material along the back of theflexible circuit electrode array 10 that is not necessary other than forbonding purposes. If there is sufficient bond with the flexible circuitelectrode array 10, it may be advantageous to thin or remove portions ofthe skirt 60 material for weight reduction.

The electrode of the present invention preferably contains platinum.Platinum can be present in any form in the electrode. The electrode haspreferably increased surface area for greater ability to transfer chargeand also having sufficient physical and structural strength to withstandphysical stress encountered in its intended use. The electrode containsplatinum having a fractal configuration so called platinum gray with anincrease in surface area of at least 5 times when compared to shinyplatinum of the same geometry and also having improved resistance tophysical stress when compared to platinum black. Platinum gray isdescribed in US 2003/0192784 “Platinum Electrode and Method forManufacturing the Same” to David Zhou, the disclosure of which isincorporated herein by reference. The electrodes of the preferredembodiment are too small to display a color without significantmagnification. The process of electroplating the surface coating ofplatinum gray comprising plating at a moderate rate, i.e., at a ratethat is faster than the rate necessary to produce shiny platinum andthat is less than the rate necessary to produce platinum black.

The flexible circuit electrode array 10 is manufactured in layers. Abase layer of polymer is laid down, commonly by some form of chemicalvapor deposition, spinning, meniscus coating or casting on a supportingrigid substrate like glass. A layer of metal (preferably platinum),preferably sandwich by layers of another metal for example titanium, isapplied to the polymer base layer and patterned to create electrodes andtraces for those electrodes. Patterning is commonly done byphotolithographic methods. The electrodes may be built up byelectroplating or similar method to increase the surface area of theelectrode and to allow for some reduction in the electrode over time.Similar plating may also be applied to the bond pads. See FIGS. 5 to 7.A top polymer layer is applied over the metal layer and patterned toleave openings for the electrodes, or openings are created later bymeans such as laser ablation. It is advantageous to allow an overlap ofthe top polymer layer over the electrodes to promote better adhesionbetween the layers, and to avoid increased electrode reduction alongtheir edges. Alternatively, multiple alternating layers of metal andpolymer may be applied to obtain more metal traces within a given width.

FIG. 12 shows an enlarged top view of the flexible circuit electrodearray 10 which is a part of the body 1 as shown for example in FIG. 5.The preferred positions of the electrodes 78 and the preferred wiring bythe trace metal 79 both embedded in the polymer 71 are shown in the FIG.12.

FIG. 13 shows a three dimensional view of a part of the flexible circuitelectrode array 10. It shows one electrode 78 which has a contact withthe trace metal 79. It also shows that the trace metal 79 overlaps theelectrode 78 and the electrode 78 overlaps the via in the polymer 71.The FIG. 13 further shows the adhesion of the polymer 71 with the tracemetal 79 and the electrode 78 which results in a very high effectiveinsulation of the trace metal 79 and the electrode 78. FIG. 13 showsalso that the trace metal 79 is preferably composed of platinumintermediate conducting layer 73 covered on the lower and upper sidepreferably with a thin titanium top conducting layer 72 a and thintitanium base conducting layer 72 b. FIG. 13 finally shows that thefirst applied base polymer 71 a and the subsequently applied top polymerlayer 71 b form a single polymer layer 71.

FIG. 14 shows melatonin levels for a first patient, PB, preoperative.The vertical axis is melatonin levels as measured with a mouth swabevery four hours. The horizontal axis is time, where the shaded portionsare normal night time hours, over a four day period. There is nosignificant increase in melatonin levels at night. In fact melatonindecreased on average during the night time periods.

FIG. 15 shows the same patient, as in FIG. 14, using the retinalprosthesis of the current invention. Melatonin levels increased, onaverage, during the night time hours.

FIG. 16 shows a second patient TB, preoperative with, on averageincreased melatonin levels at night, but inconsistent results.

FIG. 17 shows the second patent, as in FIG. 16, using the retinalprosthesis of the current invention. Melatonin level increasesignificantly, and consistently.

An alternative embodiment of the present invention can be used whensurgery is not desired due to health or surgical apprehension. Anexternal electrode can be attached to the cornea in a form similar to acontact lens, or mounted to the inside of a pair of dark glasses. Whilesuch external electrodes can not created formed vision, they can createartificial light during the daytime and be turned, or removed, to createartificial darkness at night. Such an electrode would make it possibleto control and improve the melatonin production for patients who are notnecessarily vision impaired or blind.

The present invention will be further illustrated by the followingexamples, but it is to be understood that the invention is not meant tobe limited to the details described herein.

EXAMPLES

In the present example the inventors modulate the above systemartificially through retinal prostheses in two patients with retinitispigmentosa.

Two patients TB and PB who had retinitis pigmentosa and no lightperception (NLP) for five (5) and twenty (20) years were examined. Thetwo patients and a normal control had a multiple saliva samples takenover the course of four (4) days and assayed for melatonin. The twopatients then had surgical implantation of the retinal prostheticimplant. The prosthesis was electrically stimulated in one subject. Thepatients and the normal control were then evaluated with several salivasampling over the course of four (4) days.

Melatonin concentrations in saliva samples were measured using acommercially availably melatonin ELISA assay (n=83) from ALPCODiagnostic, Windham, N.H. 03087. Concentrations were calculated byfitting to a standard logistic equation. A cosinor analysis wasperformed on the data set using commercially available software fromExpert Soft Tech.

The normal control showed typical circadian levels of melatonin withmorning peaks and day time lows with a period of 1430 minutes (24hours=1440 minutes) an about 62% rhythm.

Both patients with advanced retinitis pigmentosa showed decreasedperiodicity of melatonin levels preoperatively. Patient PB exhibited aperiod of 925 minutes with 21% rhythm. While the period could not becalculated for patient TB, he displayed 39% rhythm.

Patient PB did not show preoperative significant increase in melatoninlevels at night. In fact melatonin decreased on average during the nighttime periods as shown in the shaded normal night time hours over fourday period in FIG. 14.

Patient TB showed preoperative on average increased melatonin levels atnight, but inconsistent results as shown in the shaded normal night timehours over four day period in FIG. 16.

After surgical implantation of the retinal prosthetic, both patients PBand TB with or without prosthetic stimulation showed doubling of thepercent rhythm and a normalization of their periods 1360 and 1430minutes as would be expected from a normal circadian rhythm.

Patient PB after using the retinal prosthesis of the current inventionshowed significant increase in melatonin levels at night as shown in theshaded normal night time hours over four day period in FIG. 15.

Patient TB showed after using the retinal prosthesis of the currentinvention a significant consistent increase in melatonin levels at nightas shown in the shaded normal night time hours over four day period inFIG. 17.

The data suggest that entrainment of circadian rhythms is possible inpatients with retinitis pigmentosa, and that the retinohypothalamicpathway that modulates circadian rhythms is intact.

The data additionally suggest that it is possible to recover entrainmentof the circadian rhythm with implantation surgery.

Accordingly, an improved method making a visual prosthesis and improvedmethod of stimulating neural tissue has been shown. While the inventionhas been described by means of specific embodiments and applicationsthereof, it is understood that numerous modifications and variationscould be made thereto by those skilled in the art without departing fromthe spirit and scope of the invention. It is therefore to be understoodthat within the scope of the claims, the invention may be practicedotherwise than as specifically described herein.

1. A flexible circuit electrode array adapted to be used with a visualprosthesis, comprising: a) an insulating polymer layer comprising a toppolymer portion and a bottom polymer portion; b) at least one tracecontaining a base conducting layer, an intermediate conducting layer anda top conducting layer, embedded in said insulating polymer layerbetween said top polymer portion and said bottom polymer portion; and c)at least one electrode connected to said at least one trace through avia in said top polymer portion of said insulating polymer layer,wherein said electrode includes a first electrode portion contactingsaid trace through said via and a second electrode portion overlappingsaid trace above said top polymer portion, and wherein a region of saidtop polymer portion is defined between said trace and said secondelectrode portion, wherein the first electrode portion is a centralelectrode portion contacting a corresponding central portion of thetrace and the second electrode portion is a peripheral annular-shapedportion overlapping a corresponding peripheral annular-shaped of thetrace above said top polymer portion.
 2. The flexible circuit electrodearray of claim 1 wherein said insulating polymer layer containspolyfluorocarbons, polyethylene, polypropylene, silicone, polyamide,polyimide, liquid crystal polymer, poly-paraxylylene,polyaryletherketone and/or derivatives and/or mixtures thereof.
 3. Theflexible circuit electrode array of claim 1 wherein said intermediateconducting layer contains platinum, tantalum, iridium, palladium,rhodium, rhenium, gold, chrome, molybdenum, or carbon, or an alloythereof or a combination of two or more alloys or metal layers thereof.4. The flexible circuit electrode array of claim 1, wherein the baseconducting layer and the top conducting layers of the trace are made oftitanium, and the intermediate conducting layer is made of platinumwhereby said trace forms a titanium/platinum/titanium film stack.
 5. Theelectrode array of claim 1 wherein the at least one electrode comprisesa surface coating, said surface coating having at least 5 times thesurface area of that for the corresponding surface area resulting fromthe basic geometric shape of the electrode.
 6. The flexible circuitelectrode array of claim 1 wherein the at least one electrode comprisesa surface coating, said surface coating being biocompatible.
 7. Theflexible circuit electrode array of claim 1 wherein the at least oneelectrode comprises a surface coating, said surface coating having asurface area of less than 500 times the corresponding surface arearesulting from the basic geometric shape.
 8. The flexible circuitelectrode array of claim 1 wherein the at least one electrode comprisesa surface coating, said surface coating comprising platinum having afractal configuration, titanium nitride, iridium oxide, or mixturesthereof.
 9. The flexible circuit electrode array of claim 1, whereinsaid top polymer portion and said bottom polymer portion are made ofdifferent polymers.
 10. The flexible circuit electrode array of claim 9,wherein said top polymer portion is made of a polymer softer than thepolymer of said bottom polymer portion.
 11. The flexible circuitelectrode array of claim 10, wherein said bottom polymer portion is madeof polyimide and said top polymer portion is made of silicone.
 12. Theflexible circuit electrode array of claim 1 wherein the trace separatesthe electrode from the bottom polymer portion.
 13. The flexible circuitelectrode array of claim 1, wherein the electrode protrudes from the toppolymer portion.
 14. The flexible circuit electrode array according toclaim 1, wherein the electrode is thicker than the trace.
 15. Theflexible circuit electrode array according to claim 1, wherein the traceis wider at the electrode than it is along the rest of its length. 16.The flexible circuit electrode array according to claim 1, wherein thesecond electrode portion defines a circle coaxial to the via around thecentral electrode portion and the peripheral annular-shaped portion ofthe trace defines a circle coaxial to the via around the central portionof the trace.
 17. A flexible circuit electrode array adapted to be usedwith a visual prosthesis, comprising: a) an insulating polymer layercomprising a top polymer portion and a bottom polymer portion; b) atleast one trace containing a base conducting layer, an intermediateconducting layer and a top conducting layer, embedded in said insulatingpolymer layer between said top polymer portion and said bottom polymerportion; and c) at least one electrode connected to said at least onetrace through a via in said top polymer portion of said insulatingpolymer layer, wherein said electrode includes a first electrode portioncontacting said trace through said via and a second electrode portionoverlapping said trace above said top polymer portion, and wherein aregion of said top polymer portion is defined between said trace andsaid second electrode portion, wherein the trace includes a plate-shapedtrace portion, and wherein the first electrode portion is a centralportion contacting a central portion of the plate-shaped trace portion,and the second electrode portion is a perimeter portion overlapping aperimeter portion of the plate-shaped trace portion above said toppolymer portion, the perimeter portion of the plate-shaped trace portiondefining a closed line portion around the central portion of theplate-shaped trace portion.
 18. The flexible circuit electrode arrayaccording to claim 17, wherein the perimeter portion of the plate-shapedtrace portion is a ring-shaped or annular-shaped portion.